Functions of various tissues will be studied under conditions of altered metabolism of porphyrins and other pyrrole compounds, with special reference to functions which may be dependent on hemoprotein metabolism. Thus, (1) "renal" porphyria produced by feeding DDC to Syrian hamsters will be investigated with reference to erythropoietin production, reticulocytosis, renal filtration and absorption, etc. Renal porphyrins and hemoproteins, and enzymes involved in their biosynthesis and degradation will also be analyzed. (2) Therapeutic implications of erythropoietic activity will be investigated in patients with erythropoietic protoporphyria. (3) Recently proposed formulae for interpretation of double-isotope data (from ALA and glycine) will be investigated further in patients with various erythropoietic, hepatic, or thyroid dysfunctions. (4) Studies on fractionation of urinary pigments will be continued with reference to thyroid function (and other conditions) and characterization of these pigments as possible derivatives of non-protohemes. (5) Earlier observations on the hypoglycemic effect of hematoporphyrin given to diabetic subjects and on the effect of light and photosensitizing compounds on excretion of porphyrin will be extended with reference to the role of glucagon and insulin, and of porphyrin-binding proteins, respectively. (6) Recently developed methods will be applied to the determination of "free" versus zinc porphyrin and of porphyrinogen versus (oxidized) porphyrin in blood, tissues, and excreta of patients and experimental subjects.